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Molecular Biology of Streptomyces

Principal Investigator and
Deputy Director of Institute of Microbiology
Prof. Dr. Huarong Tan

  Tel:010-64807461
Email: Tanhr@sun.im.ac.cn

 

Differentiation and secondary metabolism of Streptomyces

Keywords: Streptomyces, secondary metabolism, differentiation, regulation

In 2007, Several genes were cloned and sequenced. Gene disruption and genetic complementation revealed that these genes were involved in metabolism and differentiation of Streptomyces.

1. The tyrosine degradation gene hppD is transcriptionally activated by HpdA and repressed by HpdR in Streptomyces coelicolor, while hpdA is negatively autoregulated and repressed by HpdR. Streptomyces coelicolor produces a brown pigment on nutrient-limited agar medium (Tyr-PM) using L-tyrosine as the sole nitrogen and carbon source. The pigment production is associated with second step of L-tyrosine catabolism catalysed by 4-hydroxyphenylpyruvate dioxygenase (HppD), which converts 4-hydroxyphenylpyruvate (4HPP) to 2,5-di hydroxyphenylacetate to provide the carbon and energy substrates for the growth of S. coelicolor on Tyr-PM. EMS and footpring experiments showed that HpdA and HpdR each bind to an overlapping region spanning the promoters of both hppD and hpdA, and that 4HPP, instead of tyrosine, is the specific ligand modulating the binding patterns. These results suggested that the transcription of hppD is subject to coarse and fine control by a complex regulatory system.

2. whiI is regulatory gene required for spore septation in the aerial mycelium of Streptomyces coelicolor. The results revealed that 45 genes were affected by the deletion of whiI. Many of these showed increased expression in the wild type at the time when aerial growth and development were taking place. About half of them showed reduced expression in the null mutant, and about half showed increased expression. Consideration of the functions of whiI-influenced genes provides some insights into the physiology of aerial hyphae.

3.sanM,sanN and sanT are essential for nikkomycin biosynthesis of Streptomyces ansochromogenes. Interaction of SanM and SanN is essential for SanM aldolase activity but not for SanN dehydrogenase activity. SanM converts piconaldehyde and 2-oxobutyrate to 4-pyridyl-2-oxo-4-hydroxyisovalerate in nikkomycin biosynthesis by interacting with SanN. SanT, a bidomain protein, is required for nikkomycin biosynthesis of Streptomyces ansochromogenes. SanT consists of ACP domain, which is post-translationally modified with phosphopantetheine (Ppant) prosthetic group at Ser-33, and AMT domain, which catalyzes the transamination of 4-pyridyl-2-oxo-4-hydroxyisovalerate (POHIV), a precursor of peptidyl moiety of nikkomycins, to pyridylhomothreonine (PHT) in vitro. The two domains function independently but both are essential for nikkomycin biosynthesis.

Group Members

Principal Investigator

Dr. Huarong Tan

Prof. Dr. Huarong Tan, Principal Investigator and Deputy Director of Institute of Microbiology, CAS, Ph. D. (1991, University of East Anglia and John Innes Centre, Norwich, UK).He is also a vice President of Chinese Society for Microbiology. The laboratory is mainly interested in molecular biology of Streptomyces. Especially, expression and regulation of genes involved in the differentiation and secondary metabolism of Streptomyces.

Professor
Dr.Gang Liu
Liug@sun.im.ac.cn

Associate Professors
Dr.Haihua Yang
Yanghh@sun.im.ac.cn

Yuqing Tian
Tianyq@sun.im.ac.cn

Research Associate
Dr Lei Li
Lil@sun.im.ac.cn

Graduate Students

Lianghui Jia,2003-2007
Hongbo Ling,2003-2007
Zhoujie Xie,2002-2007
Kun Hu,2002-2007
Yanhua Li,2004-2007
Yuanyuan Pan,2005-2008
Guohua Zhang,2005-2008
Linqi Wang,2003-2008
Guojian Liao,2006-2009
Rui Li,2004-2009
Yue Zhang,2004-2007
Liang Liang,2004-2007
Jine Li,2006-2010
Xihong He,2006-2008
Shuli Zhang,2006-2008
Gangming Xu 2007-2010
Feng Chi,2006-2010
Yang An, 2006-2009
Jing Yang, 2006-2009


Publication

  1. Gangming Xu#, Juan Wang#, Linqi Wang, Xiuyun Tian, Haihua Yang, Keqiang Fan, Keqian Yang*, and Huarong Tan*. 2010. 'Pseudo' gamma-butyrolactone receptors respond to antibiotic signals to coordinate antibiotics biosynthesis. Journal of Biological Chemistry (online) doi:10.1074/jbc.M110.143081 (# shared the first author) (IF 5.328)
  2. Haihua Yang, Yang An, Linqi Wang, Shuli Zhang, Yue Zhang, Yuqing Tian, Gang Liu, Huarong Tan*. 2010. Autoregulation of hpdR and its effect on CDA biosynthesis in Streptomyces coelicolor. Microbiology-SGM. [Epub ahead of print] (IF 3.025)
  3. Guohua Zhang, Yuqing Tian, Kun Hu, Chi Feng and Huarong Tan*. 2010. SCO3900, co-transcripted with three downstream genes, is involved in the differentiation of Streptomyces coelicolor. Current Microbiology. 60(4): 268-273 (IF 1.330)
  4. Xihong He, Rui Li, Yuanyuan Pan, Gang Liu* and Huarong Tan*. 2010. SanG, a transcriptional activator, controls nikkomycin biosynthesis through binding to the sanN-sanO intergenic region in Streptomyces ansochromogenes.  Microbioogy-SGM. 156:828 (IF 2.841)
  5. Guojian Liao, Jin’e Li, Lei Li, Haihua Yang, Yuqing Tian, Huarong Tan*. 2010. Cloning, reassembling and integration of the entire nikkomycin biosynthetic gene cluster into Streptomyces ansochromogenes lead to an improved nikkomycin production. Microbial Cell Factories. 9:6, doi:10.1186/1475- 2859-9-6 (IF 3.338)
  6. Rui Li, Gang Liu, Zhoujie Xie, Xihong He, Wenqing Chen, Zixin  Deng and Huarong Tan*. 2010. PolY, a transcriptional regulator with ATPase activity, directly activates transcription of polR in polyoxin biosynthesis in Streptomyces cacaoi. Molecular Microbiology. 75(2): 349-364. (IF 5.213)
  7. Shuli Zhang#, Bo Liu#, Haihua Yang*, Yuqing Tian, Gang Liu, Lei Li and Huarong Tan*. 2010. Characterization of EndoTT, a novel single-stranded DNA specific endonuclease from Thermoanaerobacter tengcongensis. Nucleic Acids Research. (accepted). (IF 6.878)
  8. Guojian Liao, Jin’e Li, Lei Li, Haihua Yang, Yuqing Tian and Huarong Tan*. 2009. Selectively improving nikkomycin Z production by blocking the imidazolone biosynthetic pathway of nikkomycin X and uracil feeding in Streptomyces ansochromogenes. Microbial Cell Factories. 8:61, doi:10.1186/1475-2859-8-61. (IF 3.338)
  9. Rui Li#, Zhoujie Xie#, Yuqing Tian, Haihua Yang, Wenqing Chen, Delin You, Gang Liu, Zixin Deng*, and Huarong Tan*. (2009). polR, a pathway-specific transcriptional regulatory gene, positively controls polyoxin biosynthesis in Streptomyces cacaoi var. Asoensis. Microbiology-SGM 155:1819-1831 (IF 2.841)
  10. Yuanyuan Pan#, Gang Liu#, Haihua Yang, Yuqing Tian and Huarong Tan*. (2009). The pleiotropic regulator AdpA-L directly controls the pathway-specific activator of nikkomycin biosynthesis in Streptomyces ansochromogenes. Molecular Microbiology (#shared the first author) 72(3): 710-723. (IF 5.462)
  11. Linqi Wang#, Xiuyun Tian#, Juan Wang, Haihua Yang, Keqiang Fan, Gangming Xu, Keqian Yang*, and Huarong Tan*. (2009). Autoregulation of antibiotic biosynthesis: direct binding of jadomycin to an atypical response regulator. Proceedings of the National Academy of Sciences of the United States of America (#shared the first author) 106(21): 8617-8622. (IF 9.598)
  12. Wenqing Chen, Tingting Huang, Xinyi He, Qingqing Meng, Delin You, Linquan Bai, Jialiang Li, Mingxuan Wu, Rui li, Zhoujie Xie, Huchen Zhou, Xiufen Zhou, Huarong Tan*, and Zixin Deng*. (2009).Characterization of the polyoxin biosynthetic gene cluster from Streptomyces cacaoi and engineered production of polyoxin H. The Journal of Biological Chemistry 284(16): 10627-10638 (IF 5.581)
  13. Yanhua LiJihui Zhang , Huarong Tan*.2008. Identification of a Nitroalkane oxidase gene: naoA related to the growth of Streptomyces ansochromogenes.Current Microbiology 57: 588-592. (IF 1.167)
  14. Hongbo Ling, Guojun Wang, Jin’e Li, Huarong Tan*. 2008. sanN encoding a dehydrogenase is essential for nikkomycin biosynthesis in Streptomyces ansochromogenes. Journal of Microbiology and Biotechnology 18(3):397-403. PDF (IF 2.062)
  15. Yue Zhang, Linqi Wang, Shuli Zhang, Haihua Yang* and Huarong Tan. hmgA, transcriptionally activated by HpdA, influences the biosynthesis of actinorhodin in Streptomyces coelicolor. FEMS Microbiology Letters 280:219-225.2008. PDF (IF 2.274)
  16. Liang Liang, Xihong He, Gang Liu* and Huarong Tan*. The role of a purine-specific nucleoside hydrolase in spore germination of Bacillus thuringiensis. Microbiology-SGM 154:1333-1340. 2008. PDF (IF 3.110)
  17. Haihua Yang, Linqi Wang, Zhoujie Xie, Yuqing Tian, Gang Liu, Huarong Tan*. The tyrosine degradation gene hppD is transcriptionally activated by HpdA and repressed by HpdR in Streptomyces coelicolor, while hpdA is negatively autoregulated and repressed by HpdR. Molecular Microbiology. 65 : 1064-1077, 2007.
  18. Yuqing Tian, Kay Fowler, Kim Findlay, Huarong Tan* & Keith F. Chater*. An unusual response regulator influences sporulation at early and late stages in Streptomyces coelicolor. Journal of Bacteriology. 189 : 2873-2885, 2007.
  19. Hongbo Ling, Guojun Wang, Yuqing Tian, Gang Liu and Huarong Tan*. SanM catalyzes the formation of 4-pyridyl-2-oxo-4-hydroxyiso- valerate in nikkomycin biosynthesis by interacting with SanN. Biochemical and Biophysical Research Communications. 361: 196-201, 2007.
  20. Jia Lianghui , TianYuqing, Tan Huarong*. SanT, a bidomain protein, is essential for nikkomycin biosynthesis of S. an sochromogenes. Biochemical and Biophysical Research Communications. 362: 1031-1036, 2007.
  21. Zhoujie Xie, Wenli Li, Yuqing Tian, Gang Liu & Huarong Tan*. Identification and characterization of sawC, a whiA-like gene, essential for sporulation in Streptomyces ansochromogenes. Archives of Microbiology. 188: 575-582, 2007

Patent


谭华荣 刘 钢 尼可霉素生物合成调控基因及其编码蛋白与表达工程菌. 2007. 授权号: ZL 2004 1 0058411.2.